Zinc(II)-induced self-assembly of poly-histidine-fused protein and POG peptide for protein drug controlled release
|關鍵字:||金屬誘導;自組裝;胜肽標籤;蛋白質藥物;控制釋放;Metal-induced;Self-assembly;Peptide tag;Protein drug;Controlled release|
In recent years, protein microparticles have received much attention in the drug delivery systems due to the improved protein stability and prolonged release in vivo. However, most of current preparation processes involved harsh conditions, introducing chemical crosslinkers or high salt, which often led to protein inactivation and failed to apply in drug delivery systems. In this study, we employed the well-established hexahistidine (His)-tag recombinant protein technology as well as a metal-triggerable peptide to enhance the binding strength between protein and metal ion and to fine-tune the protein drug release. The His-tagged proteins could self-assemble to form microparticles (~ 2 μm) upon zinc chloride (1 mM) treatment and an eight-hour sustained protein drug release has been achieved in physiological saline. The experimental results also indicated that by adjusting the peptide concentration and the N- and C-terminal hexahistidine-tags, the protein release could be controlled. Moreover, no protein denaturation has been observed. We have developed a universal strategy to enable facile protein microparticles fabrication under mild conditions, and their potential in release-tunable protein drug delivery systems has been successfully demonstrated.